I can already see the yawn forming: exercise again? we know it; it’s good for you, it makes you feel better because of endorphins, it makes your cardiovascular function better because it strengthens your cardiac muscle and improves your circulatory system, and it may even protect you from cancer. But have you thought about what could be the common denominator to the beneficial effects of exercise? If you did, and came up with a blank, I don’t blame you. Until recently we didn’t have a good answer, but now the outlines of an answer are forming. So here goes.

Cellular garbage

Cellular proteins get literally bent out of shape, and there are garbage collectors , called ubiquitins, that prowl the cell, bind to the misshapen proteins, bundle them into a package called proteasome, and dispose them in organelles called lysosomes, where the garbage proteins get digested. The cell, being energy-frugal, recycles the amino acids for use in the synthesis of new proteins.

A proteasome, or packaged cellular garbageProteins are not the only things that get digested.Science (January 20, 2012) highlighted the work of Beth Levine of the University of Texas Southern Medical Center in Dallas. Since 1998 she studied autophagy, which literally means “self-eating”, a process by which cells recycle used or flawed organelles, membranes and other structures. It encircles the old stuff in a double membrane, forming a sphere, and spills the contents into the same digestive vat-the lysosome. Again, the energy-conserving aspect of the process is evident. In animal experiments autophagy has also been shown to have benefits in protection from diabetes, cancer and neurodegenerative disease. Why would the cell bother with recycling? For the same reason we do: energy conservation. Amino acids uptake, protein synthesis and multimolecular cell-structure fromation are energy-guzzlers.

The exercise connection

If this self-digestion is geared to energy conservation, would it be too much of a stretch to see if it plays a role in exercise? After all, autophagy’s recycling helps cells meet energy demands. In a recent Nature paper, Levine her collaborators compared normal mice ( that’s the littlle guy, on the right) with mutant mice (on the left, by a process of elimination) that have typical background autophagy but don’t induce more when stressed or stimulated.

Skeletal muscle uses 85% of the glucose derived from food. Strenuous exercise normally lowers glucose and insulin in the bloodstream, but autophagy-impaired mice could barely do it. On the cellular level, following exercise, the autophagy-impaired mice didn’t relocate a glucose transporter to the cell membrane as do normal mice. Conclusion: autophagy is is necessary for the short-term metabolic benefits of exercise. But what about the all-important long-term effects?

Levine fattened normal mice and the autophagy-mutants, which both groups a form of diabetes, then put them through 2 months of daily treadmill workouts. Only the normal mice were able to reverse their diabetes and bring down their elevated cholesterol and triglyceride levels. The autophagy-mutants did not.

What happens on the cellular levels is just as interesting: in the skeletal muscle old mitochondria were digested by autophagy and were replaced by brand new energy-efficient ones.

The discovery of what goes on in the cells during exercise is amazing. Autophagy is critical for maintaining healthy cells. When cells contain organelles and molecules that cannot perform their respective functions the cells that contain them become sitting ducks for accumulating mutations. Before long the critical mutations for carcinogenic transformation will occur, and voilá -a cancer cell is born.

So here is one link of basic cell metabolism to cancer, diabetes, and your general health and physical fitness.

Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

1 COMMENT

Good one Dov. There are so many reasons to breath and move. Maybe instead of calling it exercise we should call it moving and breathing. The connotation might be more acceptable to most people.

Could you do a blog on the neuro-physiology of self talk. Most folks talk to themselves at a rate of 500 words per minute. Most of these thoughts are repetitive and useless. Many are negative with self criticism, old resentments and worries about the future. I believe these thoughts are the source of most mental anxiety. Why do we do this? What part of the brain does it come from? What is the neuro-physiology of self talk? In meditative yoga we learn how to stop it? Then we move our awareness to what we call the unconditioned mind. The unconditioned mind is wide open, free of criticism and judgements. It is said to be the center of our creativity and peace and calm. I find this to be true.
Jim

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